Pandemic Flu

Question 1

What three ingredients needed for pandemic?

Answer 1

1. Novel antigenicity
2. Efficient replication in human cells
3. Efficient transmission between people

Question 2

Pathogens with pandemic potential?

Answer 2

1. SARS-Cov-2
2. Influenza
3. Dengue
4. Zika
5. West Nile Virus
6. Nipath

Question 3

Name four big flu pandemics that occurred in the last 200 years.

Answer 3

1. Spanish flu (1918) - H1N1 influenza A
2. Asian flu (1957) - H2N2 influenza A
3. Hong Kong flu (1968) - H3N2 influenza A
4. Swine flu (2009) - H1N1 influenza A

Question 4

What is the natural reservoir of influenza A viruses?

Answer 4

aquatic birds

Question 5

Name the important components of an influenza virus

Answer 5

Haemagluttinin
Neuraminidase
RNA (8 segments)

Question 6

Why does influenza cause respiratory disease in humans?

Answer 6

The virus has a haemaggluttinin (HA) protein which must be cleaved for the virus to be able to fuse with the endosome membrane and release its genome into the host.

Human airway tryptase found in the lining of the lung is capable of cleaving HA.

NOTE: There are some mutated forms of influenza that do not require cleavage of HA to be able to enter host cells (these are particularly virulent)

Question 7

Why don’t all avian influenza viruses cause disease?

Answer 7

There is incompatibility with the human host allowing for enough time for immune system to clear the virus

Question 8

What protein do birds have that humans don’t that influenza viruses can co-opt?

Answer 8

ANP32

Question 9

What host protein do humans have that inhibit influenza polymerase activity?

Answer 9

Butyrophilin A3 (restriction factor)

Question 10

What mutation in the influenza polymerase gene improve compatibility with human host?

Answer 10

PB2 E627E to PB2 E627K

Question 11

Describe the influenza life cycle.

Answer 11

• The virus attaches to cells via the sialic acid receptor
• They enter through endosomes
• The acidity of the endosome triggers a fusion event by which the virus releases its genome into the host cell
• The genome travels to the nucleus and takes over host factors to drive transcription and translation
• New viral products are produced, which assemble at the surface of the cell and bud off producing hundreds of copies of the virus

Question 12

Other than a point mutation, how else can genes required for transmission into humans be acquired by viruses?

Answer 12

Reassortment - when single cells get infected by both a human and bird virus.

Their RNA will shuffle producing a bird virus that has the capability of infecting humans.
This is a quick way of viruses acquiring virulent traits - it is an example of antigenic shift

Question 13

Antigenic shift v antigenic drift?

Answer 13

Antigenic shift - abrupt and drastic changes in viral antigens (not sufficient to bring about a pandemic)
Antigenic drift - small and gradual changes in viral antigens

Question 14

What acts as a barrier to viral entry within the human respiratory tract?

Answer 14

Mucus - human viruses have evolved the ability to chop through mucus

Question 15

Difference between sialic acid linkage in humans and birds?

Answer 15

In humans it is linked to alpha2-6 but birds is almost entirely alpha 2-3

Question 16

How can a virus adapt for transmission in humans via the sialic acid receptor?

Answer 16

It acquires an affinity for human receptors and changes its haemagluttinin receptor shape

Question 17

How might airborne droplet transmission destroy a virus?

Answer 17

The concentration of respiratory secretion components will decrease - virus destroyed unless stable

Question 18

how do neuraminidase inhibitors work?

Answer 18

neuraminidase cannot cleave the receptor so virus reinfects same cell (which is dying) preventing further viral replication

Question 19

List three examples of neuraminidase inhibitors

Answer 19

Oseltamavir (tamiflu) - oral
Zanamivir (relenza) - inhaled or IV
Peramivir - IV

Question 20

List two examples of polymerase inhibitors.

Answer 20

Favipiravir
Baloxavir

Question 21

What is the role of antivirals in pandemics?

Answer 21

Used in the first 3-6 months of a pandemic

Question 22

What type of vaccine is the seasonal influenza vaccine used in high risk groups?

Answer 22

Purified fraction containing HA head of an inactivated virus

NOTE: often needs to be given with an adjuvant

Question 23

What type of flu vaccine is given to school-aged children?

Answer 23

Live-attenuated vaccine

This is a cold-adapted virus that is sprayed into the child’s nose. This provides broader and more cross-reactive immunity.

Question 24

By making reference to the structure of haemagglutinin, how could a universal flu vaccine be produced?

Answer 24

Most antibodies bind to the head of the HA molecule which is very plastic and changes every year

There is another antibody binding site on the stalk of the HA molecule, which appears to be invariant

The generation of antibodies against this invariant patch may allow antibodies to cross-react with every type of influenza (broadly-neutralising antibodies)

Question 25

What is the mechanism of action of amantidine?

Answer 25

Targets the influenza A M2 ion channel. This impairs viral replication

Question 26

What are the limitations of amantidine?

Answer 26

A single amino acid mutation (S31N) renders the virus resistant
Does not work against influenza B, pH1N1 and seasonal H3N2

Question 27

What trait must influenza viruses acquire in order to be able to successfully cause a pandemic in humans?

Answer 27

Surviving outside the host for longer - humans aren’t crammed together as much as birds/chickens etc.